E1B 55k-independent dissociation of the DNA ligase IV/XRCC4 complex by E4 34k during adenovirus infection.
The ligase IV/XRCC4 complex plays a central role in DNA double-strand break repair by non-homologous end joining (NHEJ). During adenovirus infection, NHEJ is inhibited by viral proteins E4 34k and E1B 55k, which redirect the Cul5/Rbx1/Elongin BC ubiquitin E3 ligase to polyubiquitinate and promote degradation of ligase IV. In cells infected with E1B 55k-deficient adenovirus, ligase IV could not be found in XRCC4-containing complexes and was observed in a novel ligase IV/E4 34k/Cul5/Elongin BC complex. These observations suggest that dissociation of the ligase IV/XRCC4 complex occurs at an early stage in E4 34k-mediated degradation of ligase IV and indicate a role for E4 34k in dissociation of the ligase IV/XRCCC4 complex. Expression of E4 34k alone was not sufficient to dissociate the ligase IV/XRCC4 complex, which indicates a requirement for an additional, as yet unidentified, factor in E1B 55k-independent dissociation of the ligase IV/XRCC4 complex.
Jayaram
Sumithra
S
Department of Biochemistry and Molecular Biology, Johns Hopkins University, Bloomberg School of Public Health, 615 North Wolfe Street, W-8001, Baltimore, MD 21205, USA.
Gilson
Timra
T
Ehrlich
Elana S
ES
Yu
Xiao-Fang
XF
Ketner
Gary
G
Hanakahi
Les
L
D017501:Adenovirus E1B Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017504:Adenovirus E4 Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000258:Adenovirus Infections, Human / Q000378:metabolism / Q000821:virology; D000260:Adenoviruses, Human / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D044842:Cullin Proteins / Q000737:chemistry / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000737:chemistry / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D000075065:Elongin; D017353:Gene Deletion; D005814:Genes, Viral; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D046912:Multiprotein Complexes; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
D017501:Adenovirus E1B Proteins; D017504:Adenovirus E4 Proteins; C496871:CUL5 protein, human; D044842:Cullin Proteins; D004268:DNA-Binding Proteins; D000075065:Elongin; C000607893:LIG4 protein, human; D046912:Multiprotein Complexes; D014157:Transcription Factors; C101467:XRCC4 protein, human; D011088:DNA Ligases; D000072481:DNA Ligase ATP